This project will develop the next generation of LSPR sensors based on plasmon resonance of metallic nanoprism arrays. LSPR sensors, invented and developed in the Van Duyne lab, enable high sensitivity measurement of molecular concentration and in situ characterization of binding constants. Recently LSPR sensors measured the concentration of "amyloid derived diffusable ligands" (ADDLs), a promising biomarker for and possible cause of Alzheimer's disesase, in the cerebral spinal fluid of Alzheimer's and aging controls; preliminary results showed higher levels in Alzheimer's patents and further tests are in progress. This project enhances current techniques by 1) Optimizing nanoprism shape and chemistry, and modulating binding by changing pH, temperature, and ionic strength. 2) Depositing nanoprisms onto flexible and stretchable surfaces to modulate nanoprism spacing and electromagnetic field coupling. 3) Interfacing the LSPR substrates with mass spectroscopy (MS) instruments for complimentary binding studies and MS identification. These sensors hold promise for study of ADDL chemistry, as well as for Alzheimer's diagnosis and continuing evaluation of treatment. The techniques may also be used for other biomarkers and diseases.